Impaired working memory monitoring in euthymic bipolar patients

OBJECTIVES: Converging evidence suggests that patients with remitted bipolar disorder (BD) have a persistent cognitive deficit in the executive control of working memory (WM). However, the component operations that contribute to this deficit remain unclear. The aim of the present study was to further profile the nature and specificity of WM impairment in euthymic BD. METHODS: Fifty DSM-IV-confirmed patients with euthymic BD and demographically matched controls completed a modified version of the Self-Ordered Pointing Task (SOPT) and the Cambridge Neuropsychological Test Automated Battery Pattern Recognition Test along with traditional executive and WM tasks [Stroop, initial letter Verbal Fluency (FAS), Trail-Making, Digits Forwards and Backwards]. Prospective clinical ratings over one month prior to testing confirmed that patients were euthymic at test. Absence of basal hypercortisolaemia was confirmed by serial saliva sampling. RESULTS: Error analysis revealed that whilst patients made more errors on the SOPT overall, they were no more likely to perseverate than controls. Patients' erroneous responses did not proliferate across trials, suggesting that proactive interference did not contribute to their poor performance, but serial position effects were evident where patients' errors clustered towards the end of a trial. No differences were found on the recognition memory test, in WM capacity, or on two of the three traditional executive procedures (FAS and Trail-Making). However, patients' Digits Backwards was impaired. CONCLUSIONS: These data suggest that patients with BD have a deficit in their ability to monitor the contents of WM. This deficit is not an epiphenomenon of mood, but may be due to enduring brain dysfunction, integral to bipolar illness.     

Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder

Pavuluri MN, Passarotti AM, Mohammed T, Carbray JA, Sweeney JA. Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder.
Bipolar Disord 2010: 12: 213–220. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: To examine the treatment impact of lamotrigine on the neurocognitive profile of patients with pediatric bipolar disorder (PBD). Method: Healthy controls (HC) (n = 24; mean age = 12.4 ± 3.3 years) and unmedicated PBD patients with manic, mixed, or hypomanic episodes (n = 34; mean age = 13 ± 3.1 years) were matched for IQ, age, sex, race, and socioeconomic status. A neurocognitive battery was administered at baseline and again after 14 weeks, during which PBD patients were treated with lamotrigine. Results: Clinical symptoms improved with treatment in the patient group with significant change from baseline to follow‐up on the Young Mania Rating Scale (p < 0.001) and the Children’s Depression Rating Scale–Revised (p < 0.001). Global neurocognitive function improved with lamotrigine in PBD patients over time relative to that in HC, although overall performance remained impaired. Working memory and verbal memory significantly improved with treatment in patients, and deficits in these domains were no longer significantly impaired relative to HC at follow‐up. Executive function significantly improved with treatment in the patient group but still lagged behind HC at follow‐up. Performance on attention tests did not improve with treatment. Conclusions: There appears to be significant improvement in cognitive abilities in PBD patients treated with lamotrigine that is most prominent in the areas of working memory and verbal memory and that occurs along with mood stabilization.     

Gender differences in the phenomenology of bipolar disorder

OBJECTIVES: To investigate gender differences in the phenomenology of episodes in bipolar disorder as according to ICD-10. METHODS: All patients who got a diagnosis of a manic episode/bipolar disorder in a period from 1994 to 2002 at the first outpatient treatment ever or at the first discharge from psychiatric hospitalization ever in Denmark were identified in a nationwide register. RESULTS: Totally, 682 outpatients and 1037 inpatients got a diagnosis of a manic episode/bipolar disorder at the first contact ever. Significantly more women were treated as outpatients than as inpatients. Women were treated for longer periods as inpatients but not as outpatients. In both settings, the prevalence of depressive versus manic/mixed episodes was similar for men and women and the severity of manic episodes (hypomanic /manic without psychosis/manic with psychosis) and the severity of depressive episodes (mild/moderate/severe without psychosis/severe with psychosis) did not differ between genders. The prevalence of psychotic symptoms at first contact was the same for both genders. Among patients treated in outpatient settings more men than women presented with comorbid substance abuse and among patients treated during hospitalization more women than men presented with mixed episodes. CONCLUSIONS: Besides differences in the prevalence of mixed episodes and comorbid substance abuse few gender differences are found among patients presenting with a manic episode/bipolar disorder at first contact in psychiatric inpatient or outpatient hospital settings.     

Evidence for theory of mind deficits in euthymic patients with bipolar disorder

OBJECTIVE: i) To investigate the subtle ToM (theory of mind) deficits in euthymic patients with bipolar disorder. ii) To investigate the impact of non-ToM cognitive deficits on ToM abilities. METHOD: Forty-three euthymic patients with bipolar disorder and 30 healthy control subjects were involved in this study. ToM was assessed by the Eyes test and the Hinting task. Both groups were also evaluated with a comprehensive neuropsychological battery including tasks for basic emotion and face recognition. RESULTS: The patient group was impaired on both of the ToM tasks. The patient group also showed impairment in many cognitive tasks including tasks related to sustained attention. CONCLUSION: Even euthymic patients with bipolar disorder may be impaired in advanced ToM tasks. Executive dysfunction and some other cognitives deficits such as basic emotion recognition may be at least partly responsible for this result.     

Declarative memory impairment in pediatric bipolar disorder

OBJECTIVES: Impaired verbal declarative memory has been proposed as a trait marker for adult bipolar disorder. However, similar impairments in juvenile-onset bipolar disorder have not been yet documented. Here, we assessed declarative memory in a large sample of clinically well-characterized children with bipolar disorder. METHODS: Forty-one children and adolescents with bipolar disorder [21 bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar disorder, not otherwise specified (BP-NOS)] and 17 demographically matched healthy participants completed a standardized learning and memory test. RESULTS: BP-I children recalled and recognized significantly fewer words than healthy subjects, whereas children with BP-II and BP-NOS did not differ from controls. However, individuals with BP-NOS made more perseverative errors and intrusions than the other groups. Severity of mood symptomatology was not associated with memory performance in any bipolar subtype. CONCLUSIONS: Findings suggest that declarative memory impairments in juvenile BP-I are similar to those seen in the adult form of the illness. These impairments do not appear to be secondary to clinical state; rather, they may reflect trait-related impairments. Distinct performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined phenotype is significantly heterogeneous, and may not be informative for pathogenetic investigations of bipolar disorder.     

Visuospatial working memory deficits in remitted patients with bipolar disorder: susceptibility to the effects of GABAergic agonists

Pan Y‐J, Hsieh MH, Liu S‐K. Visuospatial working memory deficits in remitted patients with bipolar disorder: susceptibility to the effects of GABAergic agonists.
Bipolar Disord 2011: 13: 365–376. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Visuospatial working memory (VSWM) deficit under high working memory (WM) load deserves further investigation as a potential trait marker for bipolar disorder (BPD). However, VSWM performances may depend on basic neurocognitive processes and are possibly compromised by neurocognitive effects of psychotropic medications. Methods: A total of 32 remitted BPD patients and 39 healthy controls undertook parametric VSWM tasks and assessments for selective attention, sustained attention, psychomotor speed, mental flexibility, and Wechsler Adult Intelligence Scale‐III full IQ. Using a multivariate model and trend analysis and controlling for other basic neurocognitive ability, the effects of mood stabilizers, antipsychotics, GABAergic agonists, and anticholinergics on VSWM performances were explored by post‐hoc analysis comparing performances across WM loads between healthy controls and patients treated and not treated with a specific medication. Results: Remitted BPD patients showed more pronounced performance declines in VSWM performances as WM loads increased, indicating inefficient VSWM processing. The VSWM deficits of remitted patients were independent of their impairments in attentional processes or psychomotor speed. Among the medications, only GABAergic agonists were associated with impaired VSWM performances. Conclusions: Remitted BPD patients had WM‐load‐dependent VSWM processing deficits after controlling for neurocognitive performances. As these deficits were associated with the use of GABAergic agonists, altered GABAergic neurotransmission might be involved with the underlying mechanisms of the impaired VSWM processing of BPD. Since GABAergic agonist use is often continued from the acute to the remitted phase in BPD and might potentially affect the functional recovery, clinicians should be aware of these neurocognitive side effects, even at low dosages. Close monitoring and timely discontinuation of GABAergic agonists is of utmost importance for clinical practice.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.     

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

OBJECTIVES: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. METHODS: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. RESULTS: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. CONCLUSIONS: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives:  Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD).
Methods:  A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment).
Results:  Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance.
Conclusions:  These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). Methods: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). Results: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short‐term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information‐processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. Conclusions: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait‐related impairments, a hypothesis that will be pursued further in longitudinal studies.     

The neurocognitive signature of psychotic bipolar disorder.

BACKGROUND: Psychotic bipolar disorder may represent a neurobiologically distinct subgroup of bipolar affective illness. We sought to ascertain the profile of cognitive impairment in patients with bipolar disorder and to determine whether a distinct profile of cognitive deficits characterizes bipolar patients with a history of psychosis. METHODS: Sixty-nine outpatients with bipolar I disorder (34 with a history of psychotic symptoms and 35 with no history of psychosis) and 35 healthy comparison subjects underwent a comprehensive neurocognitive battery. All three groups were demographically matched. RESULTS: Despite preserved general intellectual function, bipolar I patients overall showed moderate impairments on tests of episodic memory and specific executive measures (average effect size = .58), and moderate to severe deficits on attentional and processing speed tasks (average effect size = .82). Bipolar I patients with a history of psychosis were impaired on measures of executive functioning and spatial working memory compared with bipolar patients without history of psychosis. CONCLUSIONS: Psychotic bipolar disorder was associated with differential impairment on tasks requiring frontal/executive processing, suggesting that psychotic symptoms may have neural correlates that are at least partially independent of those associated with bipolar I disorder more generally. However, deficits in attention, psychomotor speed, and memory appear to be part of the broader disease phenotype in patients with bipolar disorder.     

Alterations in functional activation in euthymic bipolar disorder and schizophrenia during a working memory task

Dysfunctions in prefrontal cortical networks are thought to underlie working memory (WM) impairments consistently observed in both subjects with bipolar disorder and schizophrenia. It remains unclear, however, whether patterns of WM‐related hemodynamic responses are similar in bipolar and schizophrenia subjects compared to controls. We used fMRI to investigate differences in blood oxygen level dependent activation during a WM task in 21 patients with euthymic bipolar I, 20 patients with schizophrenia, and 38 healthy controls. Subjects were presented with four stimuli (abstract designs) followed by a fifth stimulus and required to recall whether the last stimulus was among the four presented previously. Task‐related brain activity was compared within and across groups. All groups activated prefrontal cortex (PFC), primary and supplementary motor cortex, and visual cortex during the WM task. There were no significant differences in PFC activation between controls and euthymic bipolar subjects, but controls exhibited significantly increased activation (cluster‐corrected P < 0.05) compared to patients with schizophrenia in prefrontal regions including dorsolateral prefrontal cortex (DLPFC). Although the bipolar group exhibited intermediate percent signal change in a functionally defined DLPFC region of interest with respect to the schizophrenia and control groups, effects remained significant only between patients with schizophrenia and controls. Schizophrenia and bipolar disorder may share some behavioral, diagnostic, and genetic features. Differences in the patterns of WM‐related brain activity across groups, however, suggest some diagnostic specificity. Both patient groups showed some regional task‐related hypoactivation compared to controls across the brain. Within DLPFC specifically, patients with schizophrenia exhibited more severe WM‐related dysfunction than bipolar subjects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.
Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. Methods: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. Results: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). Conclusions: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.     

Differential executive functioning performance by phase of bipolar disorder

Ryan KA, Vederman AC, McFadden EM, Weldon AL, Kamali M, Langenecker SA, McInnis MG. Differential executive functioning performance by phase of bipolar disorder. Bipolar Disord 2012: 14: 527–536. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: This study examined the influence of illness phase on executive functioning performance using factor‐derived cognitive scores in a cross‐sectional design. Methods: Healthy control (HC) subjects (n = 57), and euthymic (E‐BD) (n = 117), depressed (D‐BD) (n = 73), and hypomanic/mixed (HM/M‐BD) (n = 26) patients with bipolar disorder (BD) were evaluated using executive functioning measures (Wisconsin Card Sorting Test, Trail Making Test–Parts A and B, Verbal Fluency, Parametric Go/No‐Go, Stroop, and Digit Symbol) comprising Conceptual Reasoning and Set‐Shifting (CRSS), Processing Speed with Interference Resolution (PSIR), Verbal Fluency and Processing Speed (VFPS), and Inhibitory Control (IC) factor scores. Results: Two of the four executive functioning factors were significantly different between groups based upon phase of illness. The HM/M group was significantly worse than both of the other BD groups and the HC group in IC. The VFPS factor was sensitive to the active phase of BD, with the HM/M‐BD and D‐BD groups worse than HC. Extending our prior work, the PSIR factor, and now the CRSS factor were significantly worse in BD relative to HC, irrespective of phase of illness. Conclusions: Phase of illness had differential cognitive profiles in executive functioning factors, even after considering and excluding the impact of clinical features, illness characteristics, medications, and demographics. Consolidating executive functioning tasks into reliable factor scores provides unique information to measure and define cognitive deficiencies throughout phases of BD, and to measure intermediate phenotypes in BD, and may aid in tracking and clarifying treatment focus.     

Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction

Objectives:  Studies on neurocognitive functioning in bipolar disorder, reporting deficits in memory, attention, and executive functioning, have primarily focused on bipolar I disorder. The aim of this study was to examine whether patients with bipolar I and bipolar II disorder have different neurocognitive profiles.
Methods:  Forty-two patients with bipolar I disorder, 31 patients with bipolar II and 124 healthy controls, from a large ongoing study on psychotic disorders, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery.
Results:  The bipolar I group performed significantly poorer than the healthy control group and the bipolar II group on all measures of memory. Compared with the control group, the bipolar I group also had significantly reduced performance on most measures of attention and executive functioning, while the bipolar II group only had a significantly reduced performance on a subset of these measures. On average, 24% of the bipolar I group had clinically significant cognitive impairment (≤1.5 SD below the control group mean) across measures, compared with 13% of the bipolar II group.
Conclusions:  Patients with bipolar I and bipolar II disorder in this study have different neurocognitive profiles. Bipolar I patients have more widespread cognitive dysfunction both in pattern and magnitude, and a higher proportion has clinically significant cognitive impairments compared with patients with bipolar II. This may suggest neurobiological differences between the two bipolar subgroups.     

Spatial working memory function in twins with schizophrenia and bipolar disorder.

BACKGROUND: Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. METHODS: The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. RESULTS: Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. CONCLUSIONS: Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.     

Relational memory in psychotic bipolar disorder

Sheffield JM, Williams LE, Cohen N, Heckers S. Relational memory in psychotic bipolar disorder.
Bipolar Disord 2012: 14: 537–546. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Recent research has highlighted the phenotypic and genetic overlap of bipolar disorder and schizophrenia. Cognitive deficits in bipolar disorder parallel those seen in schizophrenia, particularly for bipolar disorder patients with a history of psychotic features. Here we explored whether relational memory deficits, which are prominent in schizophrenia, are also present in patients with psychotic bipolar disorder. Methods: We tested 25 patients with psychotic bipolar disorder on a relational memory paradigm previously employed to quantify deficits in schizophrenia. During the training, participants learned to associate a set of faces and background scenes. During the testing, participants viewed a single background overlaid by three trained faces and were asked to recall the matching face, which was either present (Match trials) or absent (Non‐Match trials). Explicit recognition and eye‐movement data were collected and compared to those for 28 schizophrenia patients and 27 healthy subjects from a previously published dataset. Results: Contrary to our prediction, we found psychotic bipolar disorder patients were less impaired in relational memory than schizophrenia subjects. Bipolar disorder subjects showed eye‐movement behavior similar to healthy controls, whereas schizophrenia subjects were impaired relative to both groups. However, bipolar disorder patients with current delusions and/or hallucinations were more impaired than bipolar disorder patients not currently experiencing these symptoms. Conclusions: We found that patients with psychotic bipolar disorder had better relational memory performance than schizophrenia patients, indicating that a history of psychotic symptoms does not lead to a significant relational memory deficit.     

Gender differences in bipolar disorder: retrospective data from the first 500 STEP-BD participants

OBJECTIVE: To examine gender differences in a large sample of patients with bipolar illness. METHODS: Exploratory analysis of baseline data from the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a multi-center NIMH project. Participants are allowed to have medical and psychiatric comorbidities, and to enter in any mood state, thus making the population more generalizable than many research cohorts. Diagnoses and history were assessed using structured clinical instruments administered by certified investigators. Given the exploratory nature of these analyses, there is no correction of for multiple comparisons. However, we emphasize findings that are statistically significant at the more stringent p < 0.01 level. RESULTS: Compared with men, women had higher rates of BPII (15.3% M versus 29.0% F, p < 0.01), comorbid thyroid disease (5.7% M versus 26.9% F, p < 0.01), bulimia (1.5% M versus 11.6% F, p < .0.01) and post-traumatic stress disorder (10.6% M versus 20.9% F, p < 0.01). Women and men had equal rates of history of lifetime rapid cycling and depressive episodes. Men were more likely to have a history of legal problems (36% M versus 17.5% F, p < 0.01). CONCLUSIONS: Potentially important gender differences in certain illness characteristics were found in our study; however, in contrast to other reports, we did not find higher rates of lifetime depressive episodes or rapid cycling in women. Although our study is limited by its retrospective study design, its results are strengthened by our large sample size and use of structured interviews.